Matrine regulates miR‐495‐3p/miR‐543/PDK1 axis to repress the progression of acute myeloid leukemia via the Wnt/β‐catenin pathway

Abstract

Acute myeloid leukemia (AML) is a commonly hematological malignancy with feature of rapidly increased immature myeloid cells in bone marrow. The anti‐tumor activity of matrine has been reported in various cancers. However, the functional role of matrine in AML progression still needs to be studied. Cell growth, apoptosis and cell cycle arrest in AML cells were evaluated using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, 5‐ethynyl‐2′‐deoxyuridine (EdU) assay and flow cytometry, respectively. The levels of adenosine triphosphate (ATP)/adenosine diphosphate (ADP) ratio, lactate production and glucose consumption were detected to evaluate glycolysis. Dual‐luciferase reporter assay was conducted to determine the relationships between phosphoinositide‐dependent kinase 1 (PDK1) and microRNA‐495‐3p (miR‐495‐3p)/microRNA‐543 (miR‐543) in AML cells. The results showed that matrine inhibited cell proliferation, glycolysis, and accelerated cell apoptosis and cell cycle arrest in AML cells. MiR‐495‐3p/miR‐543 was lowly expressed, and PDK1 was highly expressed in AML. Functionally, both miR‐495‐3p and miR‐543 could reverse the effects of matrine on cell proliferation, glycolysis, apoptosis and cell cycle arrest in AML cells. Mechanistically, miR‐495‐3p/miR‐543 directly targeted PDK1, and the inhibition impacts of miR‐495‐3p/miR‐543 on AML progression could be rescued by PDK1 overexpression. Moreover, matrine also could regulate PDK1 expression to suppress AML progression. Besides, matrine modulated miR‐495‐3p/miR‐543/PDK1 axis to inhibit the Wnt/β‐catenin pathway. In summary, matrine hampered the progression of AML through targeting miR‐495‐3p and miR‐543 to attenuate PDK1 expression, thereby repressing the Wnt/β‐catenin pathway.

Traditional Chinese medicine for acute myelocytic leukemia therapy: exploiting epigenetic targets

“…It was identified as a great anti-tumor agent on AML through the inactivation of the JAK/STAT pathway mediated by the lncRNA LINC01116/miR-592 axis ( Zhang et al, 2022 ). Similarly, Matrine inhibited the progression of AML by selectively targeting miR-495-3p and miR-543, leading to the attenuation of PDK1 expression and subsequent repression of the Wnt/β-catenin signaling pathway ( Lei et al, 2024 ).…”